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- W2885685738 abstract "Preclinical and clinical studies have validated the therapeutic potential of FGFR inhibition in urothelial bladder cancer (UBC) patients with FGFR genetic aberrations. Rogaratinib is a potent small-molecule pan-FGFR inhibitor being studied in phase I trials in UBC. Here, we studied the effects of chronic exposure of bladder cancer cells in vitro to FGFR inhibition by rogaratinib to identify changes in signaling and gene expression patterns that may identify possible drug combinations that may enhance efficacy of rogaratinib and help overcome inherent and/or acquired treatment resistance. Cell proliferation in response to rogaratinib was evaluated using crystal violet staining in a panel of 13 UBC cell lines. Continuous culture of two cell lines–JMSU1 and RT112–with either constant or increasing concentrations of rogaratinib in several independent approaches generated the resistant sublines, JMSU1-R1 to -R4 and RT112-R1 to -R4. In both cellular models rogaratinib resistance (defined as >30-fold [JMSU1] or >100-fold [RT112] difference in absolute IC50 of sublines vs. parental lines) arose reproducibly and with various treatment schedules. Morphologic changes were also observed. Transcriptomic (RNAseq) and proteomic (RD 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4781." @default.
- W2885685738 created "2018-08-22" @default.
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- W2885685738 date "2018-07-01" @default.
- W2885685738 modified "2023-09-25" @default.
- W2885685738 title "Abstract 4781: Changes in intracellular signaling following chronic FGFR inhibition in urothelial bladder cancer models" @default.
- W2885685738 doi "https://doi.org/10.1158/1538-7445.am2018-4781" @default.
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